rs6143035

chr20-62345644-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005560.6(LAMA5):c.1477+174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 644,594 control chromosomes in the GnomAD database, including 17,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4847 hom., cov: 33)
  • Exomes 𝑓: 0.22 (12785 hom.)
• Consequence: LAMA5 NM_005560.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.899

Genes affected

LAMA5 (HGNC:6485): (laminin subunit alpha 5) This gene encodes one of the vertebrate laminin alpha chains. Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. The protein encoded by this gene is the alpha-5 subunit of of laminin-10 (laminin-511), laminin-11 (laminin-521) and laminin-15 (laminin-523). [provided by RefSeq, Jun 2013]

LOC124904946 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-62345644-T-C is Benign according to our data. Variant chr20-62345644-T-C is described in ClinVar as [Benign]. Clinvar id is 1294795.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA5	NM_005560.6	c.1477+174A>G		intron_variant		ENST00000252999.7
LOC124904946	XR_007067699.1	n.149-104T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA5	ENST00000252999.7	c.1477+174A>G		intron_variant		1	NM_005560.6	P1
LAMA5	ENST00000370677.4	n.1503-59A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 37215 AN: 152058 Hom.: 4839 Cov.: 33

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.225

GnomAD4 exome AF: 0.224 AC: 110186 AN: 492418 Hom.: 12785 Cov.: 5 AF XY: 0.224 AC XY: 58706 AN XY: 262374

Gnomad4 AFR exome AF: 0.322

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.196

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.175

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.245 AC: 37245 AN: 152176 Hom.: 4847 Cov.: 33 AF XY: 0.238 AC XY: 17685 AN XY: 74404

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.222

Alfa AF: 0.230 Hom.: 1168

Bravo AF: 0.249

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.75
Dann	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6143035; hg19: chr20-60920700;